Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Exploring Amygdala Structural Changes and Signaling Pathways in Postmortem Brains: Consequences of Long-Term Methamphetamine Addiction

Version 1 : Received: 25 May 2023 / Approved: 29 May 2023 / Online: 29 May 2023 (02:51:34 CEST)
Version 2 : Received: 19 September 2023 / Approved: 19 September 2023 / Online: 20 September 2023 (03:22:53 CEST)

A peer-reviewed article of this Preprint also exists.

Azimzadeh, Z.; Omidvari, S.; Niknazar, S.; Vafaei-Nezhad, S.; Roozbahany, N.A.; Abdollahifar, M.-A.; Tahmasebinia, F.; Mahmoudiasl, G.-R.; Abbaszadeh, H.A.; Darabi, S. Exploring Amygdala Structural Changes and Signaling Pathways in Postmortem Brains: Consequences of Long-Term Methamphetamine Addiction. Anatomy & Cell Biology 2023, doi:10.5115/acb.23.193. Azimzadeh, Z.; Omidvari, S.; Niknazar, S.; Vafaei-Nezhad, S.; Roozbahany, N.A.; Abdollahifar, M.-A.; Tahmasebinia, F.; Mahmoudiasl, G.-R.; Abbaszadeh, H.A.; Darabi, S. Exploring Amygdala Structural Changes and Signaling Pathways in Postmortem Brains: Consequences of Long-Term Methamphetamine Addiction. Anatomy & Cell Biology 2023, doi:10.5115/acb.23.193.

Abstract

Methamphetamine (METH) has the potential to disrupt the activities of neurotransmitters in the Central Nervous System (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains, as well as the involvement of the CREB/BDNF and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, Real-time PCR (to measure levels of CREB, BDNF, Akt-1, GSK3, and TNF-α), Tunnel assay, stereology, and assays for ROS, GSSG, and GPX. The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX, while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH was found to induce inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

Keywords

Methamphetamine; BDNF; CREB; Akt-1; GSK3; Amygdala

Subject

Biology and Life Sciences, Toxicology

Comments (1)

Comment 1
Received: 20 September 2023
Commenter: Hojjat Allah Abbaszadeh
Commenter's Conflict of Interests: Author
Comment: revised article after reviwer comment.
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